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Cryo-electron tomography of mouse hepatitis virus: Insights into the structure of the coronavirion

Bárcena, Montserrat, Oostergetel, Gert T., Bartelink, Willem, Faas, Frank G.A., Verkleij, Arie, Rottier, Peter J.M., Koster, Abraham J., Bosch, Berend Jan
Proceedings of the National Academy of Sciences of the United States of America 2009 v.106 no.2 pp. 582-587
Murine hepatitis virus, RNA, electron microscopy, genome, models, nucleocapsid, ribonucleoproteins, tomography, transmissible gastroenteritis, virion, viruses
Coronaviruses are enveloped viruses containing the largest reported RNA genomes. As a result of their pleomorphic nature, our structural insight into the coronavirion is still rudimentary, and it is based mainly on 2D electron microscopy. Here we report the 3D virion structure of coronaviruses obtained by cryo-electron tomography. Our study focused primarily on the coronavirus prototype murine hepatitis virus (MHV). MHV particles have a distinctly spherical shape and a relatively homogenous size ([almost equal to]85 nm envelope diameter). The viral envelope exhibits an unusual thickness (7.8 ± 0.7 nm), almost twice that of a typical biological membrane. Focal pairs revealed the existence of an extra internal layer, most likely formed by the C-terminal domains of the major envelope protein M. In the interior of the particles, coiled structures and tubular shapes are observed, consistent with a helical nucleocapsid model. Our reconstructions provide no evidence of a shelled core. Instead, the ribonucleoprotein seems to be extensively folded onto itself, assuming a compact structure that tends to closely follow the envelope at a distance of [almost equal to]4 nm. Focal contact points and thread-like densities connecting the envelope and the ribonucleoprotein are revealed in the tomograms. Transmissible gastroenteritis coronavirion tomograms confirm all the general features and global architecture observed for MHV. We propose a general model for the structure of the coronavirion in which our own and published observations are combined.